The electrochemical properties of the interface between the spinel LiNi0.5Mn1.5O4-δ (LNMO4-δ) cathodes and ethylene carbonate-dimethyl carbonate (EC-DMC) electrolyte containing 1 M of LiPF6 have been investigated to achieve high-voltage durability of LNMO4-δ/graphite full cells. Coating the LNMO4-δ crystal surface by a fluoroalkylsilane self-assembled monolayer with a thickness below 2 nm resulted in a capacity retention of 94% after 100 cycles at a rate of 1 C and suppression of capacity fading for both the cathode and anode of the full cell. The observed effect is likely caused by the inhibited oxidative decomposition of EC-DMC electrolyte and vinylene carbonate (VC) species at the LNMO4-δ crystal surface and formation of a stable VC solid electrolyte interface near the anode. Moreover, the results obtained via photoelectron spectroscopy and density-functional calculations revealed that the increase in the work function of the LNMO4-δ crystal surface due to the formation of Si-O-Mn species primary contributed to the inhibition of the oxidative decomposition of the electrolyte and VC molecules at the cathode/electrolyte interface.